Nitrite testing by UPLC-MS

Has any tried utilizing UPLC-MS for the quantification of nitrites in raw materials?

I have seen papers using it to quantify the levels of nitrite in drinking water, with very low LOD and LOQ levels reported.

It would also remove the problems from chloride ions seen in standard IC analysis, and seems simpler than other techniques in terms of potential sample preparation, no derivatization required.

Or am I hoping for too much?

I think you are in the right track. The biggest problem with nitrite and nitrate analysis is the interference of chloride ions. As I used to do this for physiological fluids, I suffered a lot as I used HPLC and CEZ with 214 detection. But then I was not looking for such low levels as we are doing today. Body is full of nitrite and nitrate :slight_smile: So, in my opinion, MS as a detector would possibly be the best option to get the chloride interference out of the way. Let us know your experience.

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Nitrites as precursors of N-nitrosation in pharmaceutical samples – A trace level analysis - ScienceDirect
Perhaps this paper I recently shared in a different thread would be useful for you MarkS

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Thank you @AntoniaW

This method looks to remove the need for any pre-derivatization in the sample prep.


But I don’t know if it would work in the presence of excipients, either individually, or if trying to ascertain a level in a complete placebo formulation.

I saw this one too and wondered the same. I will ask around and find out for you if there is any data for this I can find. Typically sub ppm levels were sufficient for excipient analysis but now I understand some are looking to try screen even lower.

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@mayank.bhanti @Mrunal @AmandaGuiraldelli any insights or options explored on your side?


We do have a plan to evaluate orthogonal techniques such as the detection of derivatized nitrite and nitrate products using fluorescence, UV detectors, and mass detectors (SIM). We have not considered direct LC-MS (as reported in one of the publications on the detection of nitrite and nitrate in water) because it may be challenging to resolve different ions using reverse phase chromatography. The same was reported in the publication as well; however, they were still able to quantify different ions in SIM mode, probably because they were dealing with a water matrix. For excipients, it would be really hard to get rid of matrix interference chromatographically and matrix effect in MS ion source. We can still consider checking and determining if there would still be a way to resolve chromatographically and detect using MS.


@mayank.bhanti - thank you - I’m very far from a mass spec expert, hence my questions as I investigate all potential options.
It may be that the derivatization is the way to go from a mass spec perspective as well.

In my opinion IC (ion chromatography) can be a good choice for nitrite analysis, when using SPE for sample preparation.